Target to Non‐Target: Exploring Indoxacarb Toxicity and Resistance

Indoxacarb is a widely used oxadiazine insecticide that has a unique pro-insecticidal mode of action. It functions by metabolic activation to a sodium channel-blocking metabolite, leading to disruption of neuronal signalling and insect mortality. However, increasing evidence highlights that, beyond its target specificity, indoxacarb exerts diverse biological and environmental effects. This review provides an integrated framework linking the physicochemical properties and mode of action of indoxacarb with its toxicity, resistance development, environmental transformation and degradation while identifying key knowledge gaps and future research priorities. Indoxacarb exhibited substantial toxicity across target and non-target organisms, with reported acute LC₅₀ values ranging from 0.0521 mg/L in Labeo rohita to 5.13 μg/mL in Artemia sp., while sublethal exposure induced developmental, reproductive, behavioural, metabolic and oxidative effects. Resistance has evolved across several major pest species, with resistance levels reaching approximately 58-fold in Spodoptera litura, 472-fold in Spodoptera frugiperda, 750-fold in Plutella xylostella and 1794-fold in Tuta absoluta through mechanisms involving enhanced metabolic detoxification, reduced bioactivation, target-site mutations, sequestration and regulatory adaptations. Indoxacarb undergoes microbial, soil, plant, hydrolytic and photolytic transformation, with microbial degradation efficiencies reaching up to 95.7%-100% in some actinomycetes and approximately 68% degradation within 24 h by Priestia aryabhattai DPX-1. However, transformation does not always result in detoxification, as some metabolites, such as IN-KG433, exhibit greater toxicity than the parent compound. Overall, the evidence indicates that indoxacarb has high insecticidal efficacy with considerable ecological and resistance-related concerns. Despite extensive research, several important knowledge gaps exist, which include limited availability of field-scale data on indoxacarb degradation and remediation efficiency, insufficient information on chronic toxicity thresholds for pollinators and the absence of standardized approaches for monitoring and comparing indoxacarb resistance across pest populations. In addition, the complete molecular mechanisms underlying microbial degradation remain insufficiently characterized, particularly with respect to the genes and enzymes involved.